The present Invention relates to novel 4-fluoro-3-oxocarboxylates which are important as synthetic intermediates of aminopyrimidine derivatives (Japanese Provisional Patent Publications No. 230036/1993, No. 25187/1994, No. 116247/1994, No. 247939/1994, and No. 258223/1995) useful as an insecticide, acaricide, fungicide or nematocide, and the process for producing the same.
The 4-fluoro-3-oxocarboxylates of the present invention are novel compounds.
An object of the present invention is to provide a process for industrially producing 4-fluoro-3-oxocarboxylates which are novel compounds and important as synthetic intermediates of aminopyrimidine derivatives (Japanese Provisional Patent Publications No. 230036/1993, No. 25187/1994, No. 116247/1994, No. 247939/1994 and No. 258223/1995) useful as an insecticide, acaricide, fungicide or nematocide with a low cost and good yield.
The present inventors have studied to solve the above-mentioned problem, and as a result, they have found that 4-fluoro-3-oxocarboxylates which are novel compounds become an important synthetic intermediate for the above-mentioned useful aminopyrimidine derivatives, and established the preparation process to accomplish the present invention.
That is, the first invention relates to a 4-fluoro-3-oxocarboxylate represented by the following formula (1): 
wherein R1 represents an alkyl group or an aryl group;
R2 and R3 each represent a hydrogen atom or an alkyl group;
and R4 represents an alkyl group.
The second invention relates to a process for preparing a 4-fluoro-3-oxocarboxylate represented by the above formula 1), which comprises allowing a 2-fluorocarboxylate represented by the following formula (2): 
wherein R1 and R2 have the same meanings as defined above;
and R5 represents an alkyl group, to react with a carboxylate represented by the following formula (3): 
wherein R3 and R4 have the same meanings as defined above, in the presence of a base.
In the following, the present invention is explained in detail.
R1 to R5 in the 4-fluoro-3-oxocarboxylate (Compound (1)) which is an objective compound and in the starting materials for the preparation thereof (the compound (2) represented by the formula (2), and the compound (3) represented by the formula (3)) are as mentioned below.
As R1, there may be mentioned an alkyl group and an aryl group.
As the alkyl group of R1, there may be mentioned a straight or branched alkyl group having 1 to 10 carbon atoms; preferably 1 to 4 carbon atoms, more preferably a methyl group, an ethyl group, an n-propyl group and an n-butyl group.
As the aryl group of R1, there may be mentioned an aryl group having 6 to 10 carbon atoms; preferably a phenyl group.
As R2 and R3, there may be mentioned a hydrogen atom and an alkyl group.
As the alkyl group of R2 and R3, there may be mentioned a straight or branched alkyl group having 1 to 10 carbon atoms; preferably 1 to 4 carbon atoms. As R2, a straight alkyl group having 1 to 4 carbon atoms is preferred, and particularly preferred is a methyl group. As R3, a straight alkyl group having 1 to 4 carbon atoms is preferred, and particularly preferred is a methyl group.
As R4 and R5, there may be mentioned an alkyl group.
As the alkyl group of R4 and R5, there may be mentioned a straight or branched alkyl group having 1 to 10 carbon atoms; preferably 1 to 4 carbon atoms. As R4, a methyl group, an ethyl group or an n-butyl group is more preferred. As R5, a methyl group, an ethyl group or an n-butyl group is more preferred.
The compound (1) of the present invention is exemplified below. There may be mentioned
methyl 4-fluoro-3-oxopentanoate,
methyl 4-fluoro-3-oxohexanoate,
methyl 4-fluoro-3-oxoheptanoate,
methyl 4-fluoro-3-oxooctanoate,
methyl 4-fluoro-2-methyl-3-oxopentanoate,
methyl 4-fluoro-2-methyl-3-oxohexanoate,
methyl 4-fluoro-2-methyl-3-oxoheptanoate,
methyl 4-fluoro-2-methyl-3-oxooctanoate,
methyl 4-fluoro-4-methyl-3-oxopentanoate,
methyl 4-fluoro-4-methyl-3-oxohexanoate,
methyl 4-fluoro-4-methyl-3-oxoheptanoate,
methyl 4-fluoro-4-methyl-3-oxooctanoate,
methyl 4-fluoro-2,4-dimethyl-3-oxopentanoate,
methyl 4-fluoro-3-oxo-4-phenylbutanoate,
methyl 4-fluoro-2-methyl-3-oxo-4-phenylbutanoate,
ethyl 4-fluoro-3-oxopentanoate,
ethyl 4-fluoro-3-oxohexanoate,
ethyl 4-fluoro-3-oxoheptanoate,
ethyl 4-fluoro-3-oxooctanoate,
ethyl 4-fluoro-2-methyl-3-oxopentanoate,
ethyl 4-fluoro-2-methyl-3-oxohexanoate,
ethyl 4-fluoro-2-methyl-3-oxoheptanoate,
ethyl 4-fluoro-2-methyl-3-oxooctanoate,
ethyl 4-fluoro-4-methyl-3-oxopentanoate,
ethyl 4-fluoro-4-methyl-3-oxohexanoate,
ethyl 4-fluoro-4-methyl-3-oxoheptanoate,
ethyl 4-fluoro-4-methyl-3-oxooctanoate,
ethyl 4-fluoro-2,4-dimethyl-3-oxopentanoate,
ethyl 4-fluoro-3-oxo-4-phenylbutanoate,
ethyl 4-fluoro-2-methyl-3-oxo-4-phenylbutanoate,
propyl 4-fluoro-3-oxopentanoate,
propyl 4-fluoro-3-oxohexanoate,
propyl 4-fluoro-3-oxoheptanoate,
propyl 4-fluoro-3-oxooctanoate,
propyl 4-fluoro-2-methyl-3-oxopentanoate,
propyl 4-fluoro-2-methyl-3-oxohexanoate,
propyl 4-fluoro-2-methyl-3-oxoheptanoate,
propyl 4-fluoro-2-methyl-3-oxooctanoate,
propyl 4-fluoro-4-methyl-3-oxopentanoate,
propyl 4-fluoro-2,4-dimethyl-3-oxopentanoate,
propyl 4-fluoro-3-oxo-4-phenylbutanoate,
propyl 4-fluoro-2-methyl-3-oxo-4-phenylbutanoate,
butyl 4-fluoro-3-oxopentanoate,
butyl 4-fluoro-3-oxohexanoate,
butyl 4-fluoro-3-oxoheptanoate,
butyl 4-fluoro-3-oxooctanoate,
butyl 4-fluoro-2-methyl-3-oxopentanoate,
butyl 4-fluoro-2-methyl-3-oxohexanoate,
butyl 4-fluoro-2-methyl-3-oxoheptanoate,
butyl 4-fluoro-2-methyl-3-oxooctanoate,
butyl 4-fluoro-4-methyl-3-oxopentanoate,
butyl 4-fluoro-2,4-dimethyl-3-oxopentanoate,
butyl 4-fluoro-3-oxo-4-phenylbutanoate,
butyl 4-fluoro-2-methyl-3-oxo-4-phenylbutanoate,
isopropyl 4-fluoro-3-oxopentanoate,
isopropyl 4-fluoro-3-oxohexanoate,
isopropyl 4-fluoro-3-oxoheptanoate,
isopropyl 4-fluoro-3-oxooctanoate,
isopropyl 4-fluoro-2-methyl-3-oxopentanoate,
isopropyl 4-fluoro-2-methyl-3-oxohexanoate,
isopropyl 4-fluoro-2-methyl-3-oxoheptanoate,
isopropyl 4-fluoro-2-methyl-3-oxooctanoate,
isopropyl 4-fluoro-4-methyl-3-oxopentanoate,
isopropyl 4-fluoro-2,4-dimethyl-3-oxopentanoate,
isopropyl 4-fluoro-3-oxo-4-phenylbutanoate,
isopropyl 4-fluoro-2-methyl-3-oxo-4-phenylbutanoate,
isobutyl 4-fluoro-3-oxopentanoate,
isobutyl 4-fluoro-3-oxohexanoate,
isobutyl 4-fluoro-3-oxoheptanoate,
isobutyl 4-fluoro-3-oxooctanoate,
isobutyl 4-fluoro-2-methyl-3-oxopentanoate,
isobutyl 4-fluoro-2-methyl-3-oxohexanoate,
isobutyl 4-fluoro-2-methyl-3-oxoheptanoate,
isobutyl 4-fluoro-2-methyl-3-oxooctanoate,
isobutyl 4-fluoro-4-methyl-3-oxopentanoate,
isobutyl 4-fluoro-2,4-dimethyl-3-oxopentanoate,
isobutyl 4-fluoro-3-oxo-4-phenylbutanoate, and
isobutyl 4-fluoro-2-methyl-3-oxo-4-phenylbutanoate.
Among the compounds as mentioned above, preferred as the compound (1) are exemplified below. They are
methyl 4-fluoro-3-oxopentanoate,
methyl 4-fluoro-3-oxohexanoate,
methyl 4-fluoro-3-oxoheptanoate,
methyl 4-fluoro-3-oxooctanoate,
methyl 4-fluoro-2-methyl-3-oxopentanoate,
methyl 4-fluoro-2-methyl-3-oxohexanoate,
methyl 4-fluoro-2-methyl-3-oxoheptanoate,
methyl 4-fluoro-2-methyl-3-oxooctanoate,
methyl 4-fluoro-4-methyl-3-oxooctanoate,
methyl 4-fluoro-2,4-dimethyl-3-oxopentanoate,
methyl 4-fluoro-3-oxo-4-phenylbutanoate,
methyl 4-fluoro-2-methyl-3-oxo-4-phenylbutanoate,
ethyl 4-fluoro-3-oxopentanoate,
ethyl 4-fluoro-3-oxohexanoate,
ethyl 4-fluoro-3-oxoheptanoate,
ethyl 4-fluoro-3-oxooctanoate,
ethyl 4-fluoro-2-methyl-3-oxopentanoate,
ethyl 4-fluoro-2-methyl-3-oxohexanoate,
ethyl 4-fluoro-2-methyl-3-oxoheptanoate,
ethyl 4-fluoro-2-methyl-3-oxooctanoate,
ethyl 4-fluoro-4-methyl-3-oxopentanoate,
ethyl 4-fluoro-2,4-dimethyl-3-oxopentanoate,
ethyl 4-fluoro-3-oxo-4-phenylbutanoate,
ethyl 4-fluoro-2-methyl-3-oxo-4-phenylbutanoate,
butyl 4-fluoro-3-oxopentanoate,
butyl 4-fluoro-3-oxohexanoate,
butyl 4-fluoro-3-oxoheptanoate, and
butyl 4-fluoro-3-oxooctanoate.
The compound (2) (2-fluorocarboxylate) to be used can be easily obtained from a mesitylate of corresponding 2-hydroxycarboxylate and potassium fluoride (Tetrahedron Lett., 1993, p. 293, Tetrahedron; Asymmetry, 1994, p. 981).
The compound (3) (a starting ester represented by the formula (3)) to be used is a compound which is an industrially available.
Amounts to be used of the starting compounds are 1-fold mol or more of the compound (3) based on the amount of the compound (2); preferably 1 to 3-fold mol.
A base to be used is preferably alkali metal alkoxide such as sodium methoxide, sodium ethoxide, sodium butoxide, potassium t-butoxide, etc., and an alkali metal hydride such as lithium hydride, sodium hydride, potassium hydride, etc., more preferably sodium methoxide or sodium hydride.
An amount of the base to be used is 1-fold mol or more based on the compound (2); preferably 1 to 3-fold mol.
Synthesis of the compound (1) can be carried out without a solvent or in the presence of a solvent.
As the solvent, it is not particularly limited so long as it is not participate in the present reaction, and there may be mentioned, for example, an ether such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, etc.; an amide such as N,N-dimethylformamide, N,N-dimethylacetamide, etc.; and an aromatic hydrocarbons such as toluene, xylene, etc. And these solvents may be used singly or in combination of two or more.
An amount of the solvent to be used is 0 to 50-fold volume based on the compound (2); preferably 2 to 20-fold volume.
A temperature for synthesis of the compound (1) is 0 to 80xc2x0 C.; preferably 30 to 60xc2x0 C.
A reaction time for synthesis of the compound (1) may vary depending on the concentration, temperature and amounts to be used; and generally 0.5 to 10 hours.
The desired compound (1) prepared as mentioned above can be subjected to the conventional post-treatments such as washing, extraction, concentration, etc., and depending on necessity, can be purified by the known means such as distillation or various kinds of chromatography, etc.
From the thus obtained compound (1), aminopyrimidine derivatives useful as an insecticide, acaricide, fungicide or nematocide can be obtained.
Synthetic example of the aminopyrimidine derivatives is shown below. Incidentally, in this synthesis, methyl 4-fluoro-3-oxopentanoate which is one of the compound (1) is cyclized by formamidine and further chlorinating the 5-position and the 4-position to obtain 4,5-dichloro-6-(1-fluoroethyl)pyrimidine which is an important synthetic intermediate of useful aminopyrimidine derivatives. 